Total synthesis of racemic ajmalicine and 19‐epi‐ajmalicine

Abstract

Summaryrac.-Ajmalicine (31) and 19-epi-ajmalicine (30) have been synthesized by a convergent route from the preformed D, E-ring moieties 25 and 27 and tryptophyl bromide. Two syntheses of the trans-1 -benzoyl-3-vinyl-4-piperidineacetic acid (13), used in the preparation of 25 and 27, are also described.The alkaloids of heteroyohimbine family with normal configuration [ 11 are known to exhibit cardiovascular activities, and therefore, they have been subject of a continuous investigation by isolation from natural sources and synthesis. Ajmalicine . Optically active ajmalicine has been synthesized from naturally occurring elenolic acid [7]. In this report we describe the synthesis of' racemic ajmalicine (31) and 19-epiajmalicine (30) by assembling their molecules from the fully preformed D, E-ring moieties and tryptophyl bromide [8]. This synthetic approach is convenient for the preparation of differently substituted derivatives by using the appropriate tryptophyl bromides. The C ( 19) epimeric trans-D, E-ring moieties 25 and 27 were synthesized from the trans-l-benzoyl-3-vinyl-4-piperidine-acetic acid methyl esterThe ester 14 was obtained by two different methods, both leading to the intermediate chlorinated ester 8 (Scheme 1). In the first case [9], we started from the known trans-piperidoneacetic acid ester 1 [ 101, which was transformed in high yield to piperidineacetic acid ester 3. This was accomplished by 0-alkylation with triethyloxonium fluoroborate and reduction of the imino ether 2 with sodium borohydride. The functionalization of the ethyl side chain was effected by LofJerFreitag rearrangement: Chlorination of 3 or 4 with N-chlorosuccinimide (NCS) in ether gave in high yields the chloroamines 5 or 6, which on irradiation in trifluoro-(14). l )2,

Adiabatic interpretation of particle creation in a de Sitter universe

“…These observers (adiabatic in the remote future) will measure a non-zero number of particles in the vacuum state IO(-)). This is the Schwinger effect which would have been completely missed in the vacuum state that is de Sitter-invariant [5]. Notice the similarity between this section and section I1 as mentioned there.…”

Invariant vacuum

“…The relation between the Lewis-Riesenfeld formalism of the invariant modes and the customary formulation of the invariant wave function is not restricted to the flat DeSitter spacetime and it is indeed quite general. Let us notice that σ and τ k are nothing more the modulus and the phase of the wave function (26), and that the equations (16) and (19) are, respectively, the real and the complex parts of the wave equation (14) for the modes (26), i.e. inserting (26) in (14) one obtains (16) and (19).…”

“…Let us notice that σ and τ k are nothing more the modulus and the phase of the wave function (26), and that the equations (16) and (19) are, respectively, the real and the complex parts of the wave equation (14) for the modes (26), i.e. inserting (26) in (14) one obtains (16) and (19). Then, the customary solutions of the modes of a scalar field in a curved spacetime are recovered here by taking the appropriate solutions of σ 1 and σ 2 .…”

“…The solutions of (18) with the frequency (82) can be written in terms of the hypergeometric functions [18,26,27], or equivalently in terms of Legendre functions [7,26,28].…”

Localized particle states and dynamic gravitational effects

“…Quantized fields in de Sitter space have been studied extensively since the 1950's [12]. A thorough description of the approach used here, with references to some of the enormous literature, is given in Ref.…”